Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000573139 | SCV000660886 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-06-05 | criteria provided, single submitter | clinical testing | The p.A468V variant (also known as c.1403C>T), located in coding exon 6 of the BARD1 gene, results from a C to T substitution at nucleotide position 1403. The alanine at codon 468 is replaced by valine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Color Diagnostics, |
RCV000573139 | SCV000688120 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-06-30 | criteria provided, single submitter | clinical testing | This missense variant replaces alanine with valine at codon 468 of the BARD1 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. In an international breast cancer case-control meta-analysis, this variant was detected in 1/60466 cases and absent in 53461 controls (PMID: 33471991). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
Labcorp Genetics |
RCV000697756 | SCV000826384 | uncertain significance | Familial cancer of breast | 2023-11-14 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 468 of the BARD1 protein (p.Ala468Val). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BARD1-related conditions. ClinVar contains an entry for this variant (Variation ID: 479158). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Gene |
RCV003332199 | SCV004039939 | uncertain significance | not provided | 2023-04-02 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed in an individual with breast cancer (Dorling et al., 2021); This variant is associated with the following publications: (PMID: 18480049, 33471991) |
Baylor Genetics | RCV000697756 | SCV005054657 | uncertain significance | Familial cancer of breast | 2023-11-09 | criteria provided, single submitter | clinical testing |